Exploring the metabolic signaling network of GFPT in cancer
Abstract Metabolic homeostasis is essential for cellular function in living organisms. In cancer cells, metabolic processes are reprogrammed to meet the energy demands and biosynthetic needs for rapid growth. This reprogramming enhances nutrient flux through the glycolytic pathway, supporting ATP pr...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-08-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02687-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849226643292291072 |
|---|---|
| author | Chibuzo Sampson Pengfei Li Yiqian Wang Jing Liu Jing Lv Tian Xia Hai-long Piao Yegang Ma |
| author_facet | Chibuzo Sampson Pengfei Li Yiqian Wang Jing Liu Jing Lv Tian Xia Hai-long Piao Yegang Ma |
| author_sort | Chibuzo Sampson |
| collection | DOAJ |
| description | Abstract Metabolic homeostasis is essential for cellular function in living organisms. In cancer cells, metabolic processes are reprogrammed to meet the energy demands and biosynthetic needs for rapid growth. This reprogramming enhances nutrient flux through the glycolytic pathway, supporting ATP production and branching into pathways that synthesize macromolecules required for cell proliferation. One critical branching pathway is the hexosamine biosynthesis pathway (HBP), which, driven by metabolic reprogramming, facilitates the synthesis of uridine-5’-diphospho-N-acetylglucosamine (UDP-GlcNAc), a glycosylation substrate. This pathway is regulated by the rate-limiting enzyme glutamine-fructose-6-phosphate transaminase (GFPT), a key controller of cellular UDP-GlcNAc levels and protein glycosylation. Dysregulation of GFPT is linked to metabolic disorders, like in diabetes, and it is also frequently upregulated in cancers. Given that GFPT plays a pivotal role in cancer metabolism, elucidating its regulatory interactions with other metabolic signaling pathways under metabolic stress is crucial to identifying therapeutic vulnerabilities in cancer. This review discusses the interaction network of GFPT with other metabolic pathways, its role in nutrient sensing, and the implications of GFPT deregulation in cancer. |
| format | Article |
| id | doaj-art-5466af166f4e4b4c8d2cef34b1dc9977 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-5466af166f4e4b4c8d2cef34b1dc99772025-08-24T11:08:18ZengNature Publishing GroupCell Death Discovery2058-77162025-08-0111112010.1038/s41420-025-02687-3Exploring the metabolic signaling network of GFPT in cancerChibuzo Sampson0Pengfei Li1Yiqian Wang2Jing Liu3Jing Lv4Tian Xia5Hai-long Piao6Yegang Ma7Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and InstituteDepartment of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and InstituteDepartment of Radiotherapy, The First Affiliated Hospital of Dalian Medical UniversityDalian Institute of Chemical Physics, Chinese Academy of SciencesDalian Institute of Chemical Physics, Chinese Academy of SciencesDalian Institute of Chemical Physics, Chinese Academy of SciencesDepartment of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and InstituteDepartment of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and InstituteAbstract Metabolic homeostasis is essential for cellular function in living organisms. In cancer cells, metabolic processes are reprogrammed to meet the energy demands and biosynthetic needs for rapid growth. This reprogramming enhances nutrient flux through the glycolytic pathway, supporting ATP production and branching into pathways that synthesize macromolecules required for cell proliferation. One critical branching pathway is the hexosamine biosynthesis pathway (HBP), which, driven by metabolic reprogramming, facilitates the synthesis of uridine-5’-diphospho-N-acetylglucosamine (UDP-GlcNAc), a glycosylation substrate. This pathway is regulated by the rate-limiting enzyme glutamine-fructose-6-phosphate transaminase (GFPT), a key controller of cellular UDP-GlcNAc levels and protein glycosylation. Dysregulation of GFPT is linked to metabolic disorders, like in diabetes, and it is also frequently upregulated in cancers. Given that GFPT plays a pivotal role in cancer metabolism, elucidating its regulatory interactions with other metabolic signaling pathways under metabolic stress is crucial to identifying therapeutic vulnerabilities in cancer. This review discusses the interaction network of GFPT with other metabolic pathways, its role in nutrient sensing, and the implications of GFPT deregulation in cancer.https://doi.org/10.1038/s41420-025-02687-3 |
| spellingShingle | Chibuzo Sampson Pengfei Li Yiqian Wang Jing Liu Jing Lv Tian Xia Hai-long Piao Yegang Ma Exploring the metabolic signaling network of GFPT in cancer Cell Death Discovery |
| title | Exploring the metabolic signaling network of GFPT in cancer |
| title_full | Exploring the metabolic signaling network of GFPT in cancer |
| title_fullStr | Exploring the metabolic signaling network of GFPT in cancer |
| title_full_unstemmed | Exploring the metabolic signaling network of GFPT in cancer |
| title_short | Exploring the metabolic signaling network of GFPT in cancer |
| title_sort | exploring the metabolic signaling network of gfpt in cancer |
| url | https://doi.org/10.1038/s41420-025-02687-3 |
| work_keys_str_mv | AT chibuzosampson exploringthemetabolicsignalingnetworkofgfptincancer AT pengfeili exploringthemetabolicsignalingnetworkofgfptincancer AT yiqianwang exploringthemetabolicsignalingnetworkofgfptincancer AT jingliu exploringthemetabolicsignalingnetworkofgfptincancer AT jinglv exploringthemetabolicsignalingnetworkofgfptincancer AT tianxia exploringthemetabolicsignalingnetworkofgfptincancer AT hailongpiao exploringthemetabolicsignalingnetworkofgfptincancer AT yegangma exploringthemetabolicsignalingnetworkofgfptincancer |